The continuing overall objective of this application is to improve the understanding of early events leading to Barrett's esophagus (a risk factor for esophageal adenocarcinoma), and to identify potential targets for early intervention. Barrett's esophagus is a metaplastic change in the lining of the esophagus that is commonly considered to be a strong risk factor for and precursor to esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has been rising more rapidly than that of any malignancy in the United States for the last three decades;however, explanations for the marked incidence increase, and its marked incidence variation by ethnicity and gender (three times more common among Caucasian men than among women or African Americans) remain elusive. Obesity is a major risk factor for many cancers (including esophageal adenocarcinoma), although the mechanisms are unknown. The pathway between obesity and cancer may be through intermediary, adipose-associated hormones, such as leptin, adiponectin, ghrelin and insulin-like growth factors. These hormone systems have demonstrated experimental effects on inflammation, healing, and the risk of neoplasia and they may differ by gender and ethnicity. They therefore represent a potential mechanistic link in the individual pathway to Barrett's esophagus and may help explain why among many persons with reflux disease, only some develop Barrett's esophagus and esophageal adenocarcinoma. Thus, we propose to evaluate the associations between adipose-associated hormones, obesity, body fat distribution, and Barrett's esophagus. The specific aims of this study will be to evaluate the associations between leptin, adiponectin, and ghrelin and the risk of Barrett's esophagus, compared with GERD controls and population controls. The project will be a continuation of a recently established, high-quality, community-based case- control study of patients with a new Barrett's esophagus diagnosis, patients with gastroesophageal reflux disease, and population controls. Subjects completed detailed interviews, physical/anthropometric examinations, food frequency questionnaires, and serum samples. Serum samples are available for 99% of subjects. The proposed research will extend a highly novel translational research effort, is supported by a substantial body of literature for similar disorders, will leverage resources from an existing productive multidisciplinary research team, and may permit elucidation of an entirely new direction in determining why patients get Barrett's esophagus and esophageal adenocarcinoma. PUBLIC HEALTH RELEVANCE: Barrett's esophagus (BE) is a precancerous condition of the esophagus that is very common;it is a strong risk factor for a kind of esophageal cancer that has become much more frequent seen in recent years. The objective of this application is to improve the understanding of what causes Barrett's esophagus and identify potential targets for intervention. The proposed study explores how hormones associated with body fat may change the way the body heals after an injury, and increase the risk of cells developing precancerous changes.